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Medical Cannabis

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Cindy Chia

on 21 April 2013

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Transcript of Medical Cannabis

1. Oral
2. Inhalation (controversial) Drug Delivery Drug Delivery
Absorption
Distribution
Metabolism
Duration of Effect Basic Pharmacology Medical Purposes CB1 Receptors Major psychoactive chemical in marijuana is delta-9-tetrahydrocannabinoil (THC)

Cannabinoil and cannabidiol may also be active at high doses, which interacts with THC

Marijuana grown in different localities have different effects not wholly related to their THC content

(Grilly & Salamone, 2012) Chemicals Harry Anslinger became concerned about the change from medicinal to recreational use

Circulate stories about marijuana causing permanent brain damage, insanity, enhancing criminal & aggressive tendencies, and inducing sexual perversion (happened in 1930-1937)

(Grilly & Salamone, 2012) Federal Bureau of Narcotics Background
Chemical in Marijuana
Receptors & Brain
Brain Sites Activation
Drug Legalization
Basic Pharmacology
Drug Delivery
Absorption
Metabolism
Duration of Effect
Drug Controversies Table of Content Newer version of synthetic version of THC, Cesamet (nabilone).
Improved absorption profile Drug Delivery: Oral Prescriber’s Practice Challenges Marijuana
Mexican-Spanish word, ‘mariguana’, which means “intoxicant”
Intoxicant & medicinal herb for centuries, as far back as 2737 BC

Medicinal use gradually declined

Short ingredient shelf-life

(Grilly & Salamone, 2012) Background Cindy YF Chia Medical Cannabis Herbal form utilizing dried parts of the Cannabis plant Drug Delivery: Oral Sativex (combination of THC and cannabinoil)
Liquefied version of marijuana extract is sprayed onto the oral cavity and absorbed through mucosal tissue Drug Delivery: Oral Prescriptions for Marinol (dronabinol). Synthetic version of THC Drug Delivery: Oral (medicalmarijuana.procon.org, 2012) 11. Michigan (2008)
12. Montana (2004)
13. Nevada (2000)
14. New Jersey (2010)
15. New Mexico (2007)
16. Oregon (1998)
17. Rhode Island (2006)
18. Vermont (2004)
19. Washington (1998) 1. Alaska (1998)
2. Arizona (2010)
3. California (1996)
4. Colorado (2000)
5. Connecticut (2012)
6. Delaware (2011)
7. Hawaii (2000)
8. Maine (1999)
9. Maryland (2013)
10. Massachusetts (2012) 19 Legal Medical Marijuana States (Grilly & Salamone, 2012) Binds to CB1 cannabinoid receptors in the human brain
Mimic naturally occurring endocannabinoids produced within the brain, but with more powerful effects. THC Mode of Action CB1 is likely to have limited usefulness as a drug target due to its psychoactive activity

Alternative targets are development of CB2 receptor ligands since it regulates neural inflammation and neurogenesis, and devoid psychoactive side effects

CBD is a promising drug for neurodegenerative disorders Article’s Conclusion CB2 receptor activation

Ability to reduce microglial activation

Formation of new neurons by neurogenesis and in neurodegenerative conditions

Physiological regulator of neural progenitor cell proliferation Huntington’s Disease The endocannabinoid system expressed in the basal ganglia where it regulates neurotransmitter release and motor activity may serve as a useful target for the treatment of motor dysfunction Parkinson’s Disease Marijuana usage severely impacts short term memory, probably by interfering with the hippocampus

Deficits in spatial learning tasks, delays in matching or non-matching tests, and impaired performance in a radial arm maze in rodents. Short Term Memory Neuropathic pain associated with MS is reduced by dronabinol

Modify pain may be attributed to a CB-mediated regulation of suprespinal GABAergic and glutamatergic neurones Multiple Sclerosis (MS) Neurodegenerative Disease

Endocannabinoid tone may be enhanced in the deceased brain as protective mechanism against Aβ-induced damage Alzheimer’s Disease (AD) Purpose: To examine the various processes that the cannabinoid (CB) system in the central nervous system (CNS) control a range of neurophysiological processes such as pain, appetite, and cognition. Article Gowran, Noonan, & Campbell (2011) The Multiplicity of Action of Cannabinoids: Implications for Treating Neurodegeneration Schedule I: Not currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse. Drug Schedule Compared to other widely used drugs (alcohol, tobacco, opiates) a smaller percentage (9%) of cannabis users become dependent (Matthews, 2010)

Dependency is also less severe compared to many other legal and illegal drugs.

The withdrawal symptoms are relatively mild (Smith, 2002) Tolerance Rate Cannabis & The Brain Only through prescriptions

You’ll get a card from the doctor and present it at the dispensaries

If there are legitimate reasons on why you’re not able to travel to dispensaries, you can grow your own marijuana

Difficulties prescribing measured dosages Prescription Process Conventional marijuana may contain harmful fungus and pesticides

Burning marijuana leaves and buds can produce 50% to 70% more carcinogens than tobacco cigarettes Why is inhalation super dangerous? Oral
Inhalation (controversial) Drug Delivery Untested drug as to quality, safety and efficacy
Physician's liability around prescription and supply
Potential harm to the patient-physician relationship resulting from polarized positions
The advocacy roles of the courts and government in codifying an untested medical prescription
The disconnect in public perceptions between smoked marijuana vs smoked tobacco



(Elkashef et al., 2008) Prescriber’s Practice Challenges Medical Purposes CB1 Receptors Major psychoactive chemical in marijuana is delta-9-tetrahydrocannabinoil (THC)

Cannabinoil and cannabidiol may also be active at high doses, which interacts with THC

Marijuana grown in different localities have different effects not wholly related to their THC content

(Grilly & Salamone, 2012) Cannabinoids Harry Anslinger became concerned about the change from medicinal to recreational use

Circulate stories about marijuana causing permanent brain damage, insanity, enhancing criminal & aggressive tendencies, and inducing sexual perversion (happened in 1930-1937)

(Grilly & Salamone, 2012) Federal Bureau of Narcotics Marijuana
Mexican-Spanish word, ‘mariguana’, which means “intoxicant”
Intoxicant & medicinal herb for centuries, as far back as 2737 BC

Medicinal use gradually declined

Short ingredient shelf-life

(Grilly & Salamone, 2012) Background Background
Psychoactive Chemical
Drug Legalization
Basic Pharmacology
Drug Controversies
Tolerance Rate
Brain Sites of Action
Acute Effects
Chronic Effects
Side Effects
Efficacy
Safety
Disorders Used to Treat
Article Table of Content Cindy YF Chia Medical Cannabis Evidence concerning the benefits/risk of medical cannabis is still insufficient (darn Schedule 1!!)

Low statistically significant efficacy for cannabinoid as primary treatment of any major illness, though useful secondary agent

Risks (oral administration) appear to be relatively minor Conclusion Reduction or loss of oxygen to the cerebrum

Acute neurodegenerative insult that may arise as a consequence of stroke, trauma, and cardiac arrest

Formation of endocannabinoids is enhanced after brain injury and there is evidence that these compounds reduce the secondary damage incurred after the initial injury Cerebral Ischemia (Lamarine, 2012) Cancer
Increased likelihood of leukemia, astrocytoma & rhabdomyosarcoma in childhood through inhalation of pregnant mother. Chronic Effects (Smoked) (Lamarine, 2012) Lung damage
Smoking marijuana was found to produce an almost fivefold increase in blood carboxyhemoglobin, nearly threefold increase of inhaled tar, and retention in the lungs of 1/3 more tar as compared to smoking tobacco Chronic Effects (Smoked) (Lamarine, 2012) Relate mainly to psychological effects: Cognitive impairment, altered perception, and circulation

Physiological effect: Decrease of blood pressure

Cannabis’ interaction with other medicinal drugs, effects on cognitive function, and increased risk of heart attack. Acute Effects (Caspari, 1999) Schizophrenic patients with prior marijuana abuse had a significantly greater number of:
Re-hospitalization
Greater impairment in psychosocial function
Worsened psychopathological syndromes (thought disturbances and hostility) In relation to that.. (Lamarine, 2012) Within the range of side effects tolerated for other medicinal drugs.
Higher anxiety levels, but not necessarily anxiety disorders (cannabis withdrawal syndrome)
Decreased immune function
Higher rate of irregular heartbeat (cardiac arrhythmia)
Cerebellar infarction
Memory problems
Mood & cognitive effects Side Effects of Medical Cannabis (Marmor, 1998) Dosage Problems
THC in the preparations varies up to 10-fold, depending upon if the marijuana is made from the flowers or the whole plant

Brain Effects
Cognitive and behavioral consequences of long-term heavy marijuana use Detrimental Effects of Marijuana (Gaal et al., 2005) CB1 receptor blocker Rimonabant, brand name Accomplia, was the first selective cannabinoid receptor to be approved for use.

After just 2 years of use (2006-2008), it was concluded by the European Medicines Agency (EMEA) that "the benefits of Accomplia no longer outweighed the risks, and subsequently recommended the product be suspended from the UK market." CB1 Blocker (Audenaert et al., 2003) Researchers found evidence of deficits in endocannabinoid levels or reduced CB1 receptor function in the brains of women with anorexia nervosa.

CB1 receptor availability in the insula (a region that integrates body perception, reward and emotion, functions known to be disturbed in these patients) was affected in both anorexia and bulimia patients. Anorexia Nervosa & Bulimia (Beal et al., 1995) THC does increase the appetite (not a good thing for most of us)

For those suffering from debilitating diseases, such as AIDS-related wasting syndrome, THC has been shown to be effective in maintaining body weight Appetite (Vincent et al., 1983) THC had been shown to be effective for some patients who suffered nausea from cancer chemotherapy treatments.

However, there is a narrow window between the anti-nausea dose and that which caused unwanted psychic effects, which made THC difficult to use Anti-nausea (Kavia et al., 2010) Sativex provided some improvement in QoL indicators related to bladder dysfunction associated with MS

But the results were not statistically significant  Multiple Sclerosis (MS) (Lamarine, 2012)
Palliative care to increase Quality of Life (QoL)

Multiple Sclerosis (MS): treat symptoms such as ataxia, tremors, and spasticity

Mood enhancing psychoactive effects

Improvements in sleep and abatement of depressive symptoms

Pain management and symptoms control needs Cannabis Health Benefits (Lamarine, 2012) Data suggestive of synergistic opioid-sparing effect when combined with opiate medications

Decrease opiate medication to prevent respiratory problems

Cannabis has no overdose effect Efficacy (Lamarine, 2012) Low statistically significant efficacy as primary treatment of any major illness

Useful secondary treatment agents that contribute to Quality of Life (QOL) assessments for patients with seriously debilitating and painful conditions Efficacy (Schreiner & Dunn, 2012) Effects of cannabis generally range from 10 minutes to 8 hours, depending on the potency of the dose, other drugs consumed, route of administration, set, setting, and personal tolerance to the drug's various effects

Smoked: 2-3 hours

Oral: 4-10 hours Duration of Effect (Lamarine, 2012) Inhalation – Lung
more effective and desirable
within minutes; peak in 10-30 minutes
health burden on respiratory system Absorption http://www.cnn.com/2012/12/05/us/washington-marijuana-legalization Growing and selling marijuana will still be prosecuted as a felony

Until the state takes over managing marijuana sales, the black market will thrive as it meets consumer demands, which is illegal Controversy http://www.cnn.com/2012/12/05/us/washington-marijuana-legalization People 21 and older can:
Possess up to an ounce of marijuana, OR
16 ounces of solid, marijuana-infused product, like cookies, OR
72 ounces of infused liquid, like oil Possessions “If they can't buy it through a medical marijuana shop, which only people with a prescription and medical marijuana license can, how do they get it?" Controversies In WA & CO Canada became the first country to codify the use of herbal marijuana for medicinal purposes

Currently less than 2000 patients are federally authorized to possess medical marijuana in a population of 33 million Canadians Fun Fact: O Canada! Herbal form utilizing dried parts of the Cannabis plant Drug Delivery: Oral Newer version of synthetic version of THC, Cesamet (nabilone).
Improved absorption profile Drug Delivery: Oral Prescriptions for Marinol (dronabinol). Synthetic version of THC Drug Delivery: Oral Drug Delivery
Absorption
Distribution
Metabolism
Duration of Effect Basic Pharmacology Marijuana is not a drug itself
Refers to plant material, which contains 400 different chemicals. More than 60 of which are specific to cannabis
These chemicals are referred to cannabinoids
Most are probably not psychoactive even in high doses

(Grilly & Salamone, 2012) Facts (Lamarine, 2012) Heart disease
Carbon monoxide which interferes with hemoglobin's ability to transport oxygen to body Chronic Effects (Smoked) (Degenhardt & Hall, 2006) Examined 6 studies from 5 countries, targeting adolescents and young adults

Regular cannabis use was a predictor of increased likelihood of schizophrenia diagnosis/ symptomology
thought disturbances and hostility Side Effects: Degenhardt & Hall, 2006 (Arnone et al., 2008) Heavy cannabis users had an averaged 12% volume reduction of the hippocampus, and a 7% reduction of the amygdala compared to controls Brain Effects (Arnone et al., 2008) Arnone et al., (2008) found impaired structural integrity affecting the fiber tracts of the corpus callosum, suggesting the possibility that the structural abnormalities in the brain may underlie cognitive and behavioral consequences of long-term heavy marijuana use Brain Effects (Gaal et al., 2005) Used for obesity
It blocks the psychoactive effects of marijuana
Side effects occurred more intensely and more commonly than claimed by manufacturer
Severe depression
Suicidal thoughts Rimonabant (Piomelli et al., 2005) Scientists have discovered that blocking a marijuana-like chemical in the brain drastically increases fat burn, allowing people (OK, in the study it was mice) to eat more and exercise less without gaining weight. Diet Pills? (Merritt et al., 1980) THC has been shown to reduce intraocular pressure in laboratory animals and humans who have glaucoma

However, it was found that intraocular pressure was reduced only when patients stayed under the effects of THC almost continuously Glaucoma (Wade, Collin, Stott, and Duncombe, 2010) Meta-analysis of 3 randomized, placebo-controlled, double-blind studies

666 people with MS related spasticity

Sativex did reduce spasticity and was well tolerated by the subjects Multiple Sclerosis (MS) (Peat, 2010) Cannabinoids (Cesamet & Sativex) alone were unlikely to be helpful for MS treatment, but may offer “subjective improvement” from the patient’s perception

Smoked cannabis may see these improvements vanish if they resort to oral preparations Multiple Sclerosis (MS) (Institute of Medicine Report of 1999) Except for the harms associated with smoking, the adverse effects of marijuana use are within the range of effects tolerated for other medications. Safety (Grotenhermen, 2002) Tolerance develops to the receptor-mediated effects of THC with continued usage

Some chronic users report withdrawal symptoms after abrupt cessation (irritability, agitation, sleep disorder, and loss of appetite) Tolerance & Withdrawal (Milman et al., 2011) THC is detectable in the blood for a short time, usually a few hours, because it is rapidly metabolized into molecules known as metabolites.

At least 80 different metabolites are formed from THC. These metabolites are stored in body fat and are gradually eliminated from the body through feces and urine. Metabolism (Lamarine, 2012) Oral - GI Tract - Liver - Metabolism - Kidney
absorbed more slowly (peak in 20-30 mins)
less efficient
less health risk Absorption http://www.cnn.com/2012/12/05/us/washington-marijuana-legalization Smoking pot in public, like having an open beer could result in a civil infraction - like a ticket - but not arrest

It remains against federal law to bring any amount of marijuana onto federal property, including all federal buildings, national parks and forests, military installations and courthouses State vs Federal Law? Cigarette form
Tobacco pipes
Water Pipes Legal in Washington & Colorado for recreational use, but illegal under federal law Drug Delivery: Inhalation Healthier for your lungs
Produces highest THC content
Use less marijuana (save $$) Marijuana is heated at a high enough temperature to vaporize the THC but not burn the plant.

You can then breathe in the vapor from a bag without inhaling the harsh and potentially toxic smoke. Drug Delivery: Inhalation Edible Marijuana
Medical cannabis can be heated and made into oils, butters, and tinctures
Many cannabis clubs carry pre-made cookies, brownies, lollipops, and teas Drug Delivery: Oral Sativex (combination of THC and cannabinoil)
Liquefied version of marijuana extract is sprayed onto the oral cavity and absorbed through mucosal tissue Drug Delivery: Oral (medicalmarijuana.procon.org, 2012) 11. Michigan (2008)
12. Montana (2004)
13. Nevada (2000)
14. New Jersey (2010)
15. New Mexico (2007)
16. Oregon (1998)
17. Rhode Island (2006)
18. Vermont (2004)
19. Washington (1998) 1. Alaska (1998)
2. Arizona (2010)
3. California (1996)
4. Colorado (2000)
5. Connecticut (2012)
6. DC (2010)
7. Delaware (2011)
8. Hawaii (2000)
9. Maine (1999)
10. Massachusetts (2012) 19 Legal Medical Marijuana States (Grilly & Salamone, 2012) Binds to CB1 cannabinoid receptors in the human brain
Mimic naturally occurring endocannabinoids produced within the brain, but with more powerful effects. THC Mode of Action http://www.cnn.com/2012/12/05/us/washington-marijuana-legalization QUESTIONS? by Cindy Y. F. Chia Untested drug as to quality, safety and efficacy

Physician's liability around prescription and supply

Potential harm to the patient-physician relationship resulting from polarized positions

The advocacy roles of the courts and government in codifying an untested medical prescription

The disconnect in public perceptions between smoked marijuana vs smoked tobacco
(Elkashef et al., 2008) Facts Marijuana is not a drug itself
Refers to plant material, which contains 400 different chemicals.
More than 60 of which are specific to cannabis
These chemicals are referred to cannabinoids
Most are probably not psychoactive even in high doses

(Grilly & Salamone, 2012) Brain on Drugs: Marijuana Cannabis dependency is less determined by physical than by psychological factors Dependency (Lamarine, 2008) Drug & The Brain
Tolerance
Withdrawal
Dependency
Efficacy
Safety
Health Benefits
Disorders used to treat
Side Effects
Acute Effects
Chronic Effects
Article The word, "marijuana" derived from what language?

A. Mexican-Spanish
B. Latin-Spanish What is the medical name of marijuana?

A. Cannabinoids
B. Cannabis What is the name of one of the major psychoactive
chemical in marijuana?

A. Cannabinoids
B. Delta-9-tetrahydrocannabinoil (THC) What are the two methods of
administration of medical marijuana?

A. Oral & Inhalation
B. IV & Inhalation What is the first country to codify
the use of herbal marijuana for medicinal purposes?

A. United Kingdom
B. Canada What is the tolerance rate for marijuana use?

A. High
B. Low
Full transcript